AGCT1531 A Phase 3 Study of Active Surveillance for Low Risk and a Randomized Trial of Carboplatin vs. Cisplatin for Standard Risk Pediatric and Adult Patients with Germ Cell Tumors
An Intergroup NCTN Phase 3 Study (CTMS 17-0096)
1.1.1 To evaluate whether a strategy of complete surgical resection followed by surveillance can maintain an overall survival rate of at least 95.7% at two years for pediatric, adolescent and adult patients (ages 0- 50 years) with Stage I (low risk) malignant germ cell tumors, and at least 98% for patients with ovarian pure immature teratoma.
1.1.2 To compare the event-free survival of a carboplatin vs. cisplatin-based regimen in the treatment of pediatric, adolescent and young adult patients with standard risk germ cell tumors.
22.214.171.124 To compare the EFS of a carboplatin-based regimen (CEb) vs. a cisplatin-based regimen (PEb) in children (less than 11 years in age) with standard risk GCT.
126.96.36.199 To compare the EFS of a carboplatin-based regimen (BEC) vs. a cisplatin-based regimen (BEP) in adolescents and young adults (ages 11 - 25 years) with standard risk GCT.
1.2.1 To compare the incidence of ototoxicity in children, adolescents and young adults with standard risk germ cell tumors treated with carboplatin-based chemotherapy as compared to cisplatin-based chemotherapy.
To refine and validate a novel patient-reported measure of hearing outcomes for children, adolescents and young adults with standard risk germ cell tumors.
1.2.3 To assess the utility of using an established panel of four circulating microRNAs as a universal marker of diagnosis, recurrence and response to therapy.
1.2.4 To identify novel genetic variants associated with an increased risk of platinum-associated ototoxicity as determined by standard audiology at the end of therapy using both a candidate gene and genome wide approach.
1.3.1 To prospectively determine the correlation of tumor marker decline ( -FP and ß-HCG) with clinical outcome in low and standard risk germ cell tumor patients.
1.3.2 To prospectively determine the clinical significance of activation of the BMP, Ras/MAPK and PI3K/mTOR signaling pathways in GCTs.
1.3.3 To investigate the prognostic significance of an established panel of four circulating microRNAs at diagnosis, during follow-up and at relapse in malignant GCTs.
1.3.4 To identify integrated messenger RNA/microRNA profiles in primary malignant GCTs that correlate with poor clinical outcome.
1.3.5 To evaluate the significance of tumor DNA methylation class.
1.3.6 To characterize the incidence of nephrotoxicity in children, adolescents and young adults with standard risk germ cell tumors treated with carboplatin-based chemotherapy and treated with cisplatin-based chemotherapy.
1.3.7 To compare self-reported peripheral neuropathy and other patient-reported outcomes between children, adolescents and young adults with standard risk germ cell tumors treated with carboplatin-based chemotherapy as compared to cisplatin based chemotherapy.
1.3.8 To determine the utility of novel biomarkers of kidney tubular injury to provide earlier diagnosis of nephrotoxicity and to compare the nephrotoxicity of cisplatin versus carboplatin.
1.3.9 Identify novel genetic variants of platinum neurotoxicity, nephrotoxicity and hematologic toxicity using both a candidate gene and whole gene approach.
1.3.10 Assess the relationship between hearing loss as measured by audiometry with the effects of tinnitus as assessed on the AYA-HEARS instrument.